{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:39:44Z","timestamp":1773337184526,"version":"3.50.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cisplatin-based chemotherapy remains the standard treatment for advanced bladder cancer (BC); however, nephrotoxicity and chemoresistance limit its clinical application. Baicalin, a flavonoid metabolite derived from the botanical drug,\n                      <jats:italic>Scutellaria baicalensis Georgi<\/jats:italic>\n                      , has been reported to induces autophagy in BC. However, its regulatory effect on autophagic flux under cisplatin treatment remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We used cell counting kit (CCK)-8 and 5-ethynyl-2\u2032-deoxyuridine (EdU) assays to explore the role of baicalin in enhancing the sensitivity of BC cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      . The underlying mechanisms were explored using transmission electron microscopy, western blotting, and immunofluorescence, and these findings were validated\n                      <jats:italic>in vivo.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CCK-8 and EdU assays indicated that baicalin significantly enhanced the therapeutic effect of cisplatin and reduced its half maximal inhibitory concentration (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) value. Baicalin also inhibited the migration and invasion of BC cells. Western blotting indicated that baicalin suppressed cisplatin-induced autophagy by inhibiting autophagic flux, as evidenced by a reduction in the fusion of autophagosomes and lysosomes, along with decreased expression of lysosomal proteins LAMP1, LAMP2, CTSD, and CTSB. The results of the experiment\n                      <jats:italic>in vivo<\/jats:italic>\n                      showed that baicalin enhanced the anti-cancer effect of cisplatin. Tumor size in the combination group was significantly smaller than that in the cisplatin group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Baicalin enhanced the sensitivity of BC cells to cisplatin by inhibiting autophagic flux through lysosomal activity suppression. This study provides a potential botanical drug candidate for chemosensitization during BC chemotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1676788","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:47:49Z","timestamp":1773298069000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Baicalin chemosensitivity enhancement of cisplatin in bladder cancer via autophagy flux inhibition"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiayi","family":"Zhuang","sequence":"first","affiliation":[{"name":"Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University","place":["Zhuhai, Guangdong, China"]},{"name":"Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University","place":["Guangzhou, Guangdong, China"]},{"name":"Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haojie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University","place":["Zhuhai, Guangdong, China"]},{"name":"Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Second Affiliated Hospital of The Chinese University of HongKong\/Longgang District People\u2019s Hospital of Shenzhen","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University","place":["Zhuhai, Guangdong, China"]},{"name":"Department of Urology, The Second Affiliated Hospital of The Chinese University of HongKong\/Longgang District People\u2019s Hospital of Shenzhen","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kancheng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Urology, The First People\u2019s Hospital of Foshan","place":["Foshan, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingbo","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.eururo.2021.09.028","article-title":"Adjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and meta-analysis of individual participant data from randomised controlled trials","volume":"81","year":"2022","journal-title":"Eur. Urol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1053\/j.seminoncol.2017.10.013","article-title":"LAMPs: shedding light on cancer biology","volume":"44","author":"Alessandrini","year":"2017","journal-title":"Semin. Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41585-019-0208-0","article-title":"Molecular and histopathology directed therapy for advanced bladder cancer","volume":"16","author":"Alifrangis","year":"2019","journal-title":"Nat. Rev. Urol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1158\/2159-8290.CD-19-0292","article-title":"Targeting autophagy in cancer: recent advances and future directions","volume":"9","author":"Amaravadi","year":"2019","journal-title":"Cancer Discov."},{"key":"B5","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.eururo.2021.08.010","article-title":"European association of urology guidelines on non-muscle-invasive bladder cancer (ta, T1, and carcinoma in situ)","volume":"81","author":"Babjuk","year":"2022","journal-title":"Eur. Urol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e1901","DOI":"10.1038\/cddis.2015.283","article-title":"Haploinsufficiency of cathepsin D leads to lysosomal dysfunction and promotes cell-to-cell transmission of alpha-synuclein aggregates","volume":"6","author":"Bae","year":"2015","journal-title":"Cell. Death Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"512","DOI":"10.3390\/jpm13030512","article-title":"Bladder cancer and risk factors: data from a multi-institutional long-term analysis on cardiovascular disease and cancer incidence","volume":"13","author":"Barone","year":"2023","journal-title":"J. Pers. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3390\/jpm14040392","article-title":"Advances in urinary diversion: from cutaneous ureterostomy to orthotopic neobladder reconstruction-A comprehensive review","volume":"14","author":"Barone","year":"2024","journal-title":"J. Pers. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"B10","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1186\/s40001-024-01930-4","article-title":"Baicalin promotes the sensitivity of NSCLC to cisplatin by regulating ferritinophagy and macrophage immunity through the KEAP1-NRF2\/HO-1 pathway","volume":"29","author":"Chen","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.1158\/1078-0432.CCR-13-2060","article-title":"Autophagy inhibition augments the anticancer effects of epirubicin treatment in anthracycline-sensitive and -resistant triple-negative breast cancer","volume":"20","author":"Chittaranjan","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/s41580-023-00585-z","article-title":"Autophagy and autophagy-related pathways in cancer","volume":"24","author":"Debnath","year":"2023","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.mam.2006.08.005","article-title":"Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy","volume":"27","author":"Eskelinen","year":"2006","journal-title":"Mol. Asp. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.1091\/mbc.e04-02-0103","article-title":"Disturbed cholesterol traffic but normal proteolytic function in LAMP-1\/LAMP-2 double-deficient fibroblasts","volume":"15","author":"Eskelinen","year":"2004","journal-title":"Mol. Biol. Cell."},{"key":"B15","doi-asserted-by":"publisher","first-page":"105582","DOI":"10.1016\/j.phrs.2021.105582","article-title":"Chloroquine and hydroxychloroquine in antitumor therapies based on autophagy-related mechanisms","volume":"168","author":"Ferreira","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.4161\/auto.28594","article-title":"Development of potent autophagy inhibitors that sensitize oncogenic BRAF V600E mutant melanoma tumor cells to vemurafenib","volume":"10","author":"Goodall","year":"2014","journal-title":"Autophagy"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1080\/14786419.2024.2373955","article-title":"The therapeutic effect of baicalin in the treatment of bladder cancer: a mini-review","volume":"39","author":"Hosseini","year":"2025","journal-title":"Nat. Prod. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/sj.emboj.7601511","article-title":"LAMP proteins are required for fusion of lysosomes with phagosomes","volume":"26","author":"Huynh","year":"2007","journal-title":"EMBO J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.tips.2023.02.003","article-title":"Recent advances in targeting autophagy in cancer","volume":"44","author":"Jain","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.eururo.2023.03.029","article-title":"Epidemiology of bladder cancer in 2023: a systematic review of risk factors","volume":"84","author":"Jubber","year":"2023","journal-title":"Eur. Urol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1016\/S0140-6736(16)30512-8","article-title":"Bladder cancer","volume":"388","author":"Kamat","year":"2016","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1083\/jcb.201503075","article-title":"NBR1 enables autophagy-dependent focal adhesion turnover","volume":"212","author":"Kenific","year":"2016","journal-title":"J. Cell. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1038\/s41418-022-01004-0","article-title":"S-Nitrosylation of cathepsin B affects autophagic flux and accumulation of protein aggregates in neurodegenerative disorders","volume":"29","author":"Kim","year":"2022","journal-title":"Cell. Death Differ."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e108863","DOI":"10.15252\/embj.2021108863","article-title":"Autophagy in major human diseases","volume":"40","author":"Klionsky","year":"2021","journal-title":"EMBO J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4045","DOI":"10.1016\/j.apsb.2021.03.036","article-title":"Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1","volume":"11","author":"Kong","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"B26","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.jep.2014.08.031","article-title":"Safety, tolerability, and pharmacokinetics of a single ascending dose of baicalein chewable tablets in healthy subjects","volume":"156","author":"Li","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.3892\/or.2019.7286","article-title":"Autophagy modulation in bladder cancer development and treatment","volume":"42","author":"Li","year":"2019","journal-title":"Oncol. Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"993","DOI":"10.3892\/ijo.2013.1791","article-title":"AKT serine\/threonine protein kinase modulates baicalin-triggered autophagy in human bladder cancer T24 cells","volume":"42","author":"Lin","year":"2013","journal-title":"Int. J. Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1158\/2159-8290.CD-13-0841","article-title":"Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion","volume":"4","author":"Lock","year":"2014","journal-title":"Cancer Discov."},{"key":"B30","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1080\/15548627.2019.1637200","article-title":"Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis","volume":"16","author":"Marques","year":"2020","journal-title":"Autophagy"},{"key":"B31","doi-asserted-by":"publisher","first-page":"jcs247056","DOI":"10.1242\/jcs.247056","article-title":"The pleiotropic functions of autophagy in metastasis","volume":"134","author":"Marsh","year":"2021","journal-title":"J. Cell. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"eaav3530","DOI":"10.1126\/scisignal.aav3530","article-title":"A division of labor in mTORC1 signaling and autophagy","volume":"11","author":"Martens","year":"2018","journal-title":"Sci. Signal."},{"key":"B33","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.canlet.2019.02.035","article-title":"Cathepsin B: a sellsword of cancer progression","volume":"449","author":"Mijanovi\u0107","year":"2019","journal-title":"Cancer Lett."},{"key":"B34","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/nrc1949","article-title":"Cysteine cathepsins: multifunctional enzymes in cancer","volume":"6","author":"Mohamed","year":"2006","journal-title":"Nat. Rev. Cancer."},{"key":"B35","doi-asserted-by":"publisher","first-page":"24131","DOI":"10.1074\/jbc.M702824200","article-title":"p62\/SQSTM1 binds directly to Atg8\/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy","volume":"282","author":"Pankiv","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.3390\/cancers11101599","article-title":"Targeting autophagy for cancer treatment and tumor chemosensitization","volume":"11","author":"P\u00e9rez-Hern\u00e1ndez","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1158\/2159-8290.CD-17-0741","article-title":"A unified approach to targeting the lysosome\u2019s degradative and growth signaling roles","volume":"7","author":"Rebecca","year":"2017","journal-title":"Cancer Discov."},{"key":"B38","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12943-016-0503-9","article-title":"Over-expression of cathepsin B in hepatocellular carcinomas predicts poor prognosis of HCC patients","volume":"15","author":"Ruan","year":"2016","journal-title":"Mol. Cancer."},{"key":"B39","doi-asserted-by":"publisher","first-page":"105387","DOI":"10.1016\/j.phrs.2020.105387","article-title":"Baicalin mediated regulation of key signaling pathways in cancer","volume":"164","author":"Singh","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"101106","DOI":"10.1016\/j.mam.2022.101106","article-title":"Cathepsin S (CTSS) activity in health and disease\u2014A treasure trove of untapped clinical potential","volume":"88","author":"Smyth","year":"2022","journal-title":"Mol. Asp. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1101\/gad.2016211","article-title":"Autophagy-deficient mice develop multiple liver tumors","volume":"25","author":"Takamura","year":"2011","journal-title":"Genes. Dev."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e2347","DOI":"10.1038\/cddis.2016.243","article-title":"Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells","volume":"7","author":"Tan","year":"2016","journal-title":"Cell. Death Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41581-022-00631-7","article-title":"Cisplatin nephrotoxicity: new insights and therapeutic implications","volume":"19","author":"Tang","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1124\/jpet.114.215145","article-title":"Inhibitory effect of baicalin on collagen-induced arthritis in rats through the nuclear factor-\u03baB pathway","volume":"350","author":"Wang","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B45","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.ejphar.2019.02.023","article-title":"20(S)-ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to icotinib through inhibition of autophagy","volume":"850","author":"Wang","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1634\/theoncologist.2014-0086","article-title":"Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma","volume":"19","author":"Wolpin","year":"2014","journal-title":"Oncologist"},{"key":"B47","doi-asserted-by":"publisher","first-page":"5708","DOI":"10.1002\/ptr.7230","article-title":"Synergistic effect of combined treatment with baicalin and emodin on DSS-induced colitis in mouse","volume":"35","author":"Xu","year":"2021","journal-title":"Phytother. Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"15077","DOI":"10.1073\/pnas.2436255100","article-title":"Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor","volume":"100","author":"Yue","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B49","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.bbrc.2008.08.099","article-title":"Cathepsin D: a cellular roadmap","volume":"376","author":"Zaidi","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B50","doi-asserted-by":"publisher","first-page":"17407","DOI":"10.1038\/srep17407","article-title":"Therapeutic effect of baicalin on experimental autoimmune encephalomyelitis is mediated by SOCS3 regulatory pathway","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci. Rep."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1007\/s11434-016-1136-5","article-title":"Scutellaria baicalensis, the golden herb from the garden of Chinese medicinal plants","volume":"61","author":"Zhao","year":"2016","journal-title":"Sci. Bull. (Beijing)."},{"key":"B52","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1002\/mc.23194","article-title":"Inhibition of cathepsin D (CTSD) enhances radiosensitivity of glioblastoma cells by attenuating autophagy","volume":"59","author":"Zheng","year":"2020","journal-title":"Mol. Carcinog."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1676788\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:47:50Z","timestamp":1773298070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1676788\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":52,"alternative-id":["10.3389\/fphar.2026.1676788"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1676788","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]},"article-number":"1676788"}}